تفاعل #4127

معادلة التفاعل

N-[2-(5-bromo-1-indolinyl)-5-methylphenyl]-4-methyl-1-piperazinecarboxamide

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product

المردود 53.9%

4-Bromo-6-(4-methyl-1-piperazinyl)-9-methyl-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

المردود 53.9%

المذيبات

phosphorus oxychloride

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةat reflux for 25 minutes under nitrogen
2. 2
   درجة الحرارةThe solution was cooled
3. 3
   أخرىexcess phosphorus oxychloride was removed at 55°-60° C. under vacuum
4. 4
   درجة الحرارةIce-chilled 2N-sodium hydroxide solution (100 ml) and dichloromethane (250 ml)
5. 5
   workup.ADDITIONwere added to the residue
6. 6
   أخرىThe organic phase was separated
7. 7
   غسيلwashed with brine (2 times, 100 ml)
8. 8
   تجفيفdried over anhydrous magnesium sulfate
9. 9
   تركيزconcentrated
10. 10
    أخرىPurification
11. 11
    غسيلeluted with dichloromethane (2 l)
12. 12
    workup.ADDITIONThe fractions containing pure material
13. 13
    تركيزconcentrated
14. 14
    أخرىRecrystallization from isopropanol (30 ml)

الإجراء التجريبي

A solution of N-[2-(5-bromo-1-indolinyl)-5-methylphenyl]-4-methyl-1-piperazinecarboxamide (3.3 g, 7.68 mmoles) and phosphorus oxychloride (30 ml) was heated at reflux for 25 minutes under nitrogen. The solution was cooled and excess phosphorus oxychloride was removed at 55°-60° C. under vacuum. Ice-chilled 2N-sodium hydroxide solution (100 ml) and dichloromethane (250 ml) were added to the residue. The organic phase was separated and washed with brine (2 times, 100 ml), dried over anhydrous magnesium sulfate, and concentrated. Purification was accomplished by flash chromatography over aluminum oxide (Grade III, 100 g), eluted with dichloromethane (2 l). The fractions containing pure material were pooled and concentrated. Recrystallization from isopropanol (30 ml) yielded 1.7 g (53.9%) of product, mp 187°-189° C.

المصدر